Chapter Fifteen: Clinical Use of Diuretics, part 1

Outline Chapter 15 — Clinical Use of Diuretics

- Among most commonly used drugs

- Block NaCl reabsorption at different sites along the nephron

- The ability to induce negative balance has made them useful in multiple diseases

- Edematous states

- Hypertension

- Mechanism of action

- Three major classes

- Loop

- NaK2Cl

- Up to 25% of filtered sodium excreted

- Thiazide

- NCC

- Up to 3-5% of filtered sodium excreted

- Potassium sparing

- ENaC

- Up to 1-2% of filtered sodium excreted

- Each segment has a unique sodium channel to allow tubular sodium to flow down a concentration gradient into the cell

- Table 15-1 is interesting

- Most of the sodium 55-655 is reabsorbed in the proximal tubule

- Proximal diuretics would be highly effective if it wasn’t for the loop and other distal sites of Na absorption

- Loop Diuretics

- Furosemide

- Bumetanide

- Torsemide

- Ethacrynic acid

- NaK2Cl activated when all four sites are occupied

- Loop diuretic fits into the chloride slot

- In addition to blocking Na reabsorption results in parallel decrease in calcium resorption

- Increase in stones and nephro albinos is especially premature infants which can increase calcium excretion 10-fold

- Thiazide

- Even though they are less potent than loops they are great for hypertension

- “Not a problem in uncomplicated hypertension where marked fluid loss is neither necessary nor desirable”

- Some chlorothiazide and metolazone also inhibit carbonic anhydrase in the proximal tubule

- Increase Calcium absorption. Mentions that potassium sparing diuretics do this also

- Potassium sparing diuretics

- Amiloride

- Spironolactone

- Triamterene

- Act at principal cells in the cortical collecting tubule,

- Block aldosterone sensitive Na channels.

- Discusses the difference between amiloride and triamterene and spiro

- Mentions that trimethoprim can have a similar effect

- Spiro is surprisingly effective in cirrhosis and ascites

- Talks about amiloride helping in lithium toxicity

- Partially reverse and prevent NDI from lithium

- Trial Terence as nephrotoxin?

- Causes crystaluria and casts

- These crystals are pH independent

- Faintly radio opaque

- Acetazolamide

- Blocks carbonic anhydrase

- Causes both NaCl and NaHCO3 loss

- Modest diuresis de to distal sodium reclamation

- Mannitol

- Nonreabsorbable polysaccharide

- Acts mostly in proximal tubule and Loop of Henle

- Causes water diuresis

- Was used to prevent ATN

- Can cause hyperosmolality directly and through the increased water loss

- This hyperosmolality will be associated with osmotic movement of water from cells resulting in hyponatremia, like in hyperglycemia.

- Docs must treat the hyperosmolality not the hyponatremia

- Time course of Diuresis

- Efficacy of a diuretic related to

- Site of action

- Dietary sodium action

- 15-1 shows patient with good short diuretic response but other times of low urine Na resulting in no 24 hour net sodium excretion.

- Low sodium diets work with diuretics to minimize degree of sodium retension while diuretic not working

- Also minimizes potassium losses

- Increase frequency

- Increase dose

- What causes compensatory anti-diuresis

- Activation of RAAS and SNS

- ANG II, aldo, norepi all promote Na reabsorption

- But even when prazosin to block alpha sympathetic and capto[pril to block RAAS sodium retention occurs

- Decrease in BP retains sodium with reverse pressure natriuresis

- Even with effective diuresis there is reestablishment of a new steady state

- Diuresis is countered by

- Increases in tubular reabsorption at non-diuretic sensitive sites (neurohormonal mediated)

- Flow mediated in creases i